Precise base editing with CC context-specificity using engineered human APOBEC3G-nCas9 fusions.

ABSTRACT:

Background

Cytidine base editors (CBEs), composed of a cytidine deaminase fused to Cas9 nickase (nCas9), enable efficient C-to-T conversion in various organisms. However, current base editors can induce unwanted bystander C-to-T conversions when multiple Cs are present in the ~ 5-nucleotide activity window of cytidine deaminase, which negatively affects their precision. Here, we develop a new base editor which significantly reduces unwanted bystander activities.

Results

We used an engineered human APOBEC3G (eA3G) C-terminal catalytic domain with preferential cytidine-deaminase activity in motifs with a hierarchy CCC>CCC>CC (where the preferentially deaminated C is underlined), to develop an eA3G-BE with distinctive CC context-specificity and reduced generation of bystander m

SUBMITTER: Liu Z 

PROVIDER: S-EPMC7461344 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature